Integrated approaches reveal determinants of genome-wide binding and function of the transcription factor Pho4.
Integrated approaches reveal determinants of genome-wide binding and function of the transcription factor Pho4.
复制标题
综合方法揭示了转录因子PHO4的全基因组结合和功能的决定因素。
DOI：
10.1016/j.molcel.2011.05.025
复制
发表时间：
2011-06-24
期刊：
影响因子：
16
通讯作者：
O'Shea EK
中科院分区：
文献类型：
--
作者：
Zhou X;O'Shea EK
转录因子与DNA的结合是控制基因表达的关键调控步骤。对转录因子具有高亲和力的DNA序列在基因组中比受这些因子结合或调节的基因的实例更频繁地出现。虽然已经确定了几种影响转录调控特异性的机制，但尚不清楚这些机制是否可以解释所观察到的给定转录因子的全基因组结合或调控模式。我们使用全基因组方法来研究反式影响如何塑造Pho 4的结合和调控景观，Pho 4是一种芽殖酵母转录因子，可激活基因表达以应对磷酸盐限制。我们发现，核小体显着限制的网站Pho 4绑定。在核小体耗尽位点，Pho 4和另一种转录因子Cbf 1之间的竞争决定了Pho 4的占有率，提高了Pho 4在磷酸盐充足条件下的转录激活阈值，并防止Pho 4在磷酸盐饥饿期间激活磷酸盐调节子之外的基因。Pho 4结合不足以转录激活-转录因子Pho 2和Pho 4之间的合作相互作用特异性地发生在被激活的基因上。结合这些实验观察，我们能够在全球范围内预测Pho 4结合及其功能。我们的研究为序列特异性转录因子的全局控制机制提供了新的见解。
Binding of transcription factors to DNA is a key regulatory step in the control of gene expression. DNA sequences with high affinity for transcription factors occur more frequently in the genome than instances of genes bound or regulated by these factors. Although several mechanisms have been identified that influence the specificity of transcriptional regulation, it is not known if these can explain the observed genome-wide pattern of binding or regulation for a given transcription factor. We used genome-wide approaches to study how trans influences shape the binding and regulatory landscape of Pho4, a budding yeast transcription factor that activates gene expression in response to phosphate limitation. We find that nucleosomes significantly restrict the sites to which Pho4 binds. At nucleosome-depleted sites, competition between Pho4 and another transcription factor, Cbf1, determines Pho4 occupancy, raising the threshold for transcriptional activation by Pho4 in phosphate replete conditions and preventing Pho4 activation of genes outside the phosphate regulon during phosphate starvation. Pho4 binding is not sufficient for transcriptional activation – a cooperative interaction between the transcription factor Pho2 and Pho4 occurs specifically at genes that are activated. Combining these experimental observations, we are able to globally predict Pho4 binding and its functionality. Our study provides insights into the mechanisms of global control by sequence-specific transcription factors.
登录
查看更多内容
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
16
作者：
Badis, Gwenael;Chan, Esther T.;van Bakel, Harm;Pena-Castillo, Lourdes;Tillo, Desiree;Tsui, Kyle;Carlson, Clayton D.;Gossett, Andrea J.;Hasinoff, Michael J.;Warren, Christopher L.;Gebbia, Marinella;Talukder, Shaheynoor;Yang, Ally;Mnaimneh, Sanie;Terterov, Dimitri;Coburn, David;Yeo, Ai Li;Yeo, Zhen Xuan;Clarke, Neil D.;Lieb, Jason D.;Ansari, Aseem Z.;Nislow, Corey;Hughes, Timothy R.
通讯作者：
Hughes, Timothy R.
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
56.9
作者：
Maerkl, Sebastian J.;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
7
作者：
Graumann, J;Dunipace, LA;Deshaies, RJ
通讯作者：
Deshaies, RJ